S. cerevisiae was chosen as a host for the development of a model system, which tested the effectiveness of antisense as a mechanism of controlling gene expression. The reporter gene chosen for this study is the a-amylase gene from Bacillus licheniformis. S. cerevisiae has no endogenous a-amylase activity. The sense and antisense gene copies were introduced into the yeast cell in various combinations, initially with the primary objective of obtaining an excess of antisense to sense transcripts. In several of the yeast recombinant strains used in this study the a-amylase gene (sense or antisense) was integrated into one of the yeast chromosomes. Despite achieving a copy number difference of 9:2, and a reasonably favourable mRNA ratio (4:1), together with temporal coincidence of the two transcript populations, no down-regulation of a amylase was observed. In these initial experiments a complete copy of the a amylase antiscript had been used. It was considered that the lack of any observable antisense effect may have partly been due to poor interactions between the two complementary a-amylase sequences. One of the critical requirements to achieving an antisense effect is that the two complementary RNA molecules be available to base pair with one another. This requirement would not be met if the antisense RNA molecule, when synthesised, was forming stable intramolecular structures. With this in mind, several truncated forms of the gene were tested for their ability to downregulate a-amylase expression. Northern analysis of the mRNA population from these yeast recombinant strains yielded the expected sized RNA products. These truncated anti-mRNA molecules appeared to be reasonably stable (relative to the a-amylase mRNA itself), and present in an abundance similar to that found for the complete gene antisense transcript (3-4:1). However, none of these truncated antisense molecules were found to exert an antisense effect. In an effort to improve the spatial coincidence of the two RNA populations, the two a-amylase genes (sense and antisense), were introduced on separate episomal plasmids.Additionally, a more favourable ratio of antisense to sense transcripts was obtained (7.5:1) by placing the antisense gene under the control of the inducible GAL1 promoter, while the sense remained under the control of the AdHl promoter. This experimental system resulted in a 12% reduction in the levels of a-amylase activity. The final set of experiments presented involved the construction of a chimeric sense-antisense fusion (referred to as the cis construct), in such a way that, upon transcription, a fusion RNA product would be produced consisting of the complete a-amylase message tagged to a-amylase antisense sequences. This construct was designed to maximise the co-localisation of the two RNAs (sense and antisense) by linking their transcription and cellular distribution. Upon introduction and subsequent transcription of this gene fusion in yeast cells, a complete inhibition of a-amylase enzyme activity was achieved. Interestingly, Northern analysis revealed a shorter, but discrete transcript than that predicted. The particular location of this construct, whether episomal or chromosomal, was found not to alter the outcome.