In previous studies, we have reported that the intraperitoneal (i.p.) injection of HIV-1 infected human U937 cells into normal mice resulted in long-term persistence of anti-HIV antibodies and in a small percentage (10-20%) of HIV-1 infected animals at 6-12 months after the injection. The study reported here was undertaken to detect T immune defects in U937-HIV-1-injected mice. Eight months after the initial injection, a marked decrease in DTH response against U937 cells was detected in HIV injected animals. In addition, a consistent decrease in DTH response against a soluble mannoprotein antigen of Candida albicans cell wall (MP-F2) was also observed in U937-HIV-1-injected mice, chronically infected with low-virulent strain of the fungus. No decreases in DTH response was observed in control-injected animals. These data indicate that U937-HIV-1-injected mice become unable to mount a normal antigen-specific immune response. Although the mechanisms involved in the generation of these T cell defects remain unclear, these events appear to be somehow related to the HIV-1 infection and should be considered in the current studies of HIV-1 infection with transgenic mice.