TrkC is a receptor tyrosine kinase that is activated by neurotrophin-3, a factor important in the development of certain areas of the central nervous system. We have cloned and sequenced the human trkC cDNA and found that the predicted amino acid sequence is 97 to 98% homologous to the rat and porcine trkC sequences, respectively. The rat trkC has several isoforms due to alternative splicing in the tyrosine kinase domain. We cloned one human splice variant that has a nucleic acid sequence identical to the rat isoform with an insert of 14 amino acids. The human trkC cDNA also has a (CGG)n repeat in the 5'-untranslated region. This sequence was not highly polymorphic in that 79 of 80 chromosomes examined had eight repeats, while 1 chromosome had four repeats. By PCR analysis of a somatic cell hybrid panel and fluorescence in situ hybridization with the cDNA clone, human trkC was mapped to chromosome 15q24-q25.