LAT-1/CD98 amino acid transporter expression and activity are induced in hepatic cells deprived of arginine. The promoter dependency of this regulation was investigated. LAT-1 expression, in contrast to that of CD98 heavy chain 4F2, was actinomycin D sensitive in cells cultured without arginine. Transient transfection analysis with promoter reporter constructs including the 2 kbp LAT-1 promoter or a sub-sequence containing multiple potential amino acid response elements failed to show significant amino acid sensitivity in various cell types. Chromatin-dependency did not appear to account for this result as hepatic cell clones stably transfected with the promoter constructs showed little or no arginine or leucine responsive promoter activity. These studies suggest that while amino acid sensitivity of LAT-1 expression is transcriptionally regulated, cis elements within the proximal promoter do not directly mediate this regulation. Understanding mechanisms by which this gene responds to amino acid availability will contribute to our knowledge of how eukaryotic cells sense and respond to their environment.