The possible role of Isl-1 in insulin-gene transcription was investigated using Northern blot analysis to determine whether insulin and Isl-1 gene expression are correlated in various somatic cell hybrids. Among several hybrid cell lines obtained by fusing insulin-producing rat insulinoma (RIN) cells and mouse spleen cells, three (RR2, RR5, and RR11) had amounts of insulin transcripts similar to those of the parental RIN cells, although two of them, RR5 and RR11, lacked Isl-1 protein. In contrast, two RIN x mouse L cell hybrids where insulin expression was extinct still expressed Isl-1. RT-PCR analysis showed that Isl-1 transcripts are widely distributed in various mouse tissues, including pancreas, brain, lung, thymus, and ovary. These results indicate that Isl-1 is not essential for insulin gene expression.