Ochratoxin A (OA) has been reported to affect immune function both at the level of antibody synthesis and natural killer (NK) cell activity. In the present study we demonstrate that exposure of purified human lymphocyte populations and subpopulations to the toxin will abrogate the cells' ability to respond to activating stimuli in vitro. Thus, both IL-2 production and IL-2 receptor expression of activated T lymphocytes are severely impaired. When the cells are preincubated with the analogue ochratoxin B (OB) prior to OA exposure, the inhibitory effect of OA is reversed. Furthermore, the inhibitory effect of OA on antibody production is not only due to blocking of T helper cell function. Highly purified B lymphocytes will not respond to polyclonal activators in vitro after a brief pulse with OA. The results strongly suggest that the toxin causes its immunosuppression through interference with essential processes in cell metabolism irrespective of lymphocyte population or subpopulation.