The carcinogenicity of nickel subsulfide (alpha Ni3S2) was studied following intrarenal (i.r.) injection in rats. Within 100 weeks after i.r. injection of 5 mg of alpha Ni3S2, renal cancers were found in 64 percent of Wistar-Lewis rats, 50 percent of NIH Black rats, 28 percent of Fischer rats and 0 percent of Long-Evans rats. These findings demonstrate significant differences in susceptibilities of the four rat strains to alpha Ni3S2-induction of renal cancers. No renal cancers were found in male Fischer rats that received i.r. injection of alpha Ni3S2 in dosages of 0.6, 1.2 or 2.5 mg. In male Fischer rats that received i.r. injection of alpha Ni3S2 in dosages of 5 or 10 mg, the incidences of renal cancers were 28 percent and 75 percent, respectively. These findings demonstrate a dose response relationship for alpha Ni3S2-induction of renal cancers. In male Fischer rats that received i.r. injection of 10 mg of alpha Ni3S2 combined with 6.9 mg of Mn dust, the incidence of renal cancers was 32 percent, which differed significantly from the corresponding incidences of 75 percent and 0 percent in rats that received i.r. injections of only alpha Ni3S2 (10 mg) or Mn dust (6.9 mg). These findings demonstrate that alpha Ni3S2-induction of renal cancers is inhibited by simultaneous administration of manganese dust. The 54 renal tumors that were found in this study were all malignant, and distant metastases were present in 69 percent of tumor-bearing rats. The histogenesis of alpha Ni3S2-induced renal tumors from epithelial or mesenchymal progenitor cells could not be definitely established.