The ability of two purified, particulate hepatitis B virus antigens to induce antibodies and delayed cutaneous hypersensitivity responses was studied in Hartley guinea pigs. Hepatitis B surface antigen (HBsAg) was purified by several methods from the plasmas of human, chronic HBsAg carriers, while hepatitis B core antigen (HBcAg) was purified from chimpanzee liver by ultracentrifugation. Guinea pigs immunized with the HBsAg preparations developed anti-HBs in the absence of anti-HBc but delayed cutaneous hypersensitivity reactions to HBsAg were seen clearly only in animals immunized with high doses of the most highly purified HBsAg preparation. Guinea pigs immunized with the HBcAg preparation developed anti-HBc in the absence of anti-HBs, and showed delayed cutaneous hypersensitivity reactions to HBcAg in the absence of reactions to a chimpanzee liver-derived control antigen. No skin reactivity was seen to HBcAg in guinea pigs immunized with HBsAg. Similarly, guinea pigs immunized with HBcAg showed no skin reactivity to HBsAg. It was concluded that both HBsAg and HBcAg are capable of inducing distinct humoral and cell-mediated immune responses in Hartley guinea pigs.