Adult male Sprague-Dawley rats were given 0, 0.02, 0.05, and 0.1% nickel sulfate (NiSO4-6H2O) or 0, 44.7, 111.75, and 223.5 mg Ni/L, respectively, in their drinking water for 13 wk. Twenty-four hours following the end of such treatment, all animals survived and no apparent clinical signs of toxicity were noted. The final mean body weights of various nickel sulfate-treated rats were not significantly decreased except for the 0.1% nickel sulfate treated group when compared to those in the control. The absolute and relative organ weights were either increased or decreased or remained unchanged, depending on the organ and the dose of nickel sulfate. Total plasma proteins, plasma albumin and globulins, and plasma glutamic pyruvic transaminase activity were all significantly decreased in 0.1% nickel sulfate-treated rats. Lymphocyte subpopulations (T and B cells) were induced at lower dose levels, but suppressed at the highest (0.1%) dose group. A significant decrease in urine volume and an increase in BUN were observed at the highest dose group. Biochemical analysis of bronchoalveolar lavage fluid and lung tissue showed some lung damage, whereas no damage to the testis or DNA in liver and kidneys were found. No gross or microscopic changes were seen in any of the various tissues examined. The relative order of bioaccumulation of nickel in different organs of rats when treated at 0.1% nickel sulfate (223.5 mg Ni/L) was kidneys > testes > lung = brain > spleen > heart = liver. But with regard to order of toxicity, both immune and pulmonary systems were found to be very sensitive targets, followed by kidney.