A human fetal liver cDNA library was screened at reduced hybridization stringency for v-raf-related sequences. In addition to the expected c-raf-1 cDNA, a second sequence was isolated. Comparison of the second gene (pks) to the other raf-related sequences revealed nucleotide homologies of 71%. The predicted amino acid sequence of the kinase domain is sufficiently similar to that of v-raf to suggest that pks may encode a polypeptide that exhibits serine/threonine kinase activity. The expression of pks mRNA (2.7 kilobases long) is elevated in peripheral blood mononuclear cells isolated from two patients with angioimmunoblastic lymphadenopathy with dysproteinemia, a disease in which autoantibodies are produced following the lymphoproliferative activation of B cells. Analysis of somatic cell hybrids for segregation of the pks locus revealed the presence of an additional locus closely related to the pks sequence.