Male CD-1 mice were exposed to 10, 100 or 1000 ppm vinyl chloride (VC) for 2--8 weeks at 6 hr/day, 5 days/week. A slight increase in the spleen weight of mice was noted at the highest exposure level. Spleens were obtained from these animals (4 mice/group after 2, 4, and 8 weeks of exposure) and their lymphocytes cultured in vitro with or without the presence of phytomitogens, phytohemagglutinin (PHA) and pokeweed mitogen (PWM). Relative blast formation and the DNA synthesis was measured by the incorporation of 3H-thymidine in the cultured cells. The response of splenic lymphocytes to the phytomitogens was increased several-fold by VC exposure. The effects were apparent at 1000 ppm VC after 2 weeks of exposure and at all levels of VC exposure after 4--8 weeks. The effects were generally more pronounced at 100 ppm VC exposure than those at 1000 ppm. In vitro culture of splenic lymphocytes from control or VC-exposed mice in the VC atmosphere did not show an enhancement of blast formation. Alteration of VC metabolism during the VC exposure in vivo yielded results that indicated that metabolites of VC may be responsible for the stimulation of lymphocyte transformation observed in splenic cultures.