Peripheral blood mononuclear cells (PBMC) from Saanen goats experimentally infected with the lentivirus caprine arthritis-encephalitis virus (CAEV) were evaluated by semiquantitative reverse transcriptase PCR for gamma interferon (IFN-gamma), interleukin-4 (IL-4), and IL-2 gene expression following in vitro stimulation with purified CAEV gp135 surface protein (SU). Studies examined three goats with chronic arthritis and four clinically asymptomatic goats at 5 years postinfection. SU-responsive IFN-gamma mRNA-positive cells and IL-4 mRNA-positive cells in PBMC from infected goats reflected differences in lymphokine balance associated with disease status. IFN-gamma mRNA-positive cells were dominant in PBMC from asymptomatic goats, whereas SU-responsive IL-4 mRNA-positive cells were dominant in PBMC from goats with arthritis. IL-2 gene expression was not responsive to SU stimulation of PBMC from either asymptomatic or arthritic goats. Lymphokine mRNA profiles in SU-stimulated PBMC were dependent on the presence of CD4+ T lymphocytes. The results indicate that asymptomatic goats have a dominant population of CAEV SU-reactive T-helper 1 (Th1)-like lymphocytes in PBMC whereas goats with clinical arthritis have a dominant population of SU-reactive Th2-like lymphocytes.