Pigment (macromelanophore) patterns in the platyfish Xiphophorus maculatus are due to a complex pigmentary locus; for example, the spotted-dorsal (Sd) fin pattern is due to the Sd locus. In interspecific backcross hybrids with the swordtail X. helleri, the Sd pattern changes into benign or malignant dorsal fin melanoma as a result of hemi- or homozygous loss of a platyfish regulatory (R) gene, the tumor suppressor gene Diff, that appears to play a role in the final differentiation of macromelanophores. Closely linked to the pigmentary locus is an epidermal growth factor receptor-like gene, Xmrk-2, that has arisen by duplication from the linked Xmrk-1. The transcriptional expression of the Xmrk genes was determined in various tissues including Sd pigment patterns and melanomas of various growth potential using reverse transcription-polymerase chain reaction. While Xmrk-1 expression was found in all tissues examined, Xmrk-2 expression correlated with pigment cell growth. Xmrk-2 was highly expressed in the dorsal fin exhibiting the Sd pattern but drastically reduced in a platyfish mutant which has lost the capacity to form these pigment cells in the dorsal fin. Most interestingly, Xmrk-2 expression increased with the proliferative capacity of the melanomas but declined once melanoma growth ceased. We conclude that Xmrk-2 plays a role in the formation of the pigment pattern cell type, perhaps in proliferation of precursor cells, which, in melanoma, are kept in a proliferative state due to loss of Diff.(ABSTRACT TRUNCATED AT 250 WORDS)