We have examined the RNA expression pattern for the Drosophila calmodulin gene during embryogenesis by in situ hybridization to transcripts in whole embryos. Our results indicate that maternally derived calmodulin mRNA is homogeneously distributed throughout the early embryo, but that these maternal transcripts are lost by maximal germ band extension. Zygotic transcription of the gene in mid- to late-stage embryos is restricted to neural cell precursors and their progeny in both the central and peripheral nervous systems. Thus, activation of calmodulin transcription during embryonic development appears to mark a commitment to a neural fate. Northern blot analysis revealed that the two transcripts from the calmodulin gene are differentially expressed during embryogenesis. Comparison of Northern blot and in situ hybridization data indicates that the longer calmodulin mRNA is a nervous tissue-specific transcript. This suggests that neural-specific regulation of polyadenylation site usage occurs. We have also examined calmodulin expression in embryos homozygous for mutations in four loci which are known to affect nervous system development: numb, the achaete-scute complex, daughterless, and mastermind. The calmodulin transcription pattern is altered in embryos mutant for each of these loci, suggesting that regulation by these genes, either directly or indirectly, is taking place.