The effect of hydrocortisone (HCO) on pokeweed mitogen (PWM)-driven Ig production from human tonsil B- plus T-lymphocyte cocultures was analyzed. IgM and IgG production decreased in cultures with a B/T ratio of 10/1 or higher (P less than 0.001) and increased in cultures with a B/T ratio of 1/1 or lower (P less than 0.01) when 10(-5) M HCO was added. Similar effects were observed on Ig production from peripheral blood lymphocyte cultures. These effects were only obtained at the HCO doses of 10(-5) and 10(-6) M, and no modifications by monocyte depletion were observed. The function of HCO-pretreated B cells did not differ from that of control B cells when cocultured with fresh T cells. However, the HCO pretreatment of T cells before coculturing with fresh B cells affected the Ig production in the same way as the addition of the drug to fresh cocultures. These results suggest that HCO modulates the PWM-driven Ig production by affecting helper and suppressor T-cell activity.