Patients with lung cancer (LC) have a reduced T-cell proliferative response to phytohemagglutinin (PHA) compared with that of healthy individuals. This decreased response is a result of an inhibitory effect exerted by the monocytes as evidenced by: (1) a restoration to normal levels of the response to PHA when the peripheral blood mononuclear cells were depleted of adherent cells (AD) and (2) a dose-dependent inhibition of the response to PHA when the nonadherent cell population was co-cultured with increasing numbers of autologous AD cells. The addition of indomethacin to the cultures resulted in only a partial restoration of the response to PHA. Monocyte production of interleukin-1 from patients with LC in response to lipopolysaccharide was normal. These findings support the hypothesis that the AD cell population plays a major role in the low T-cell proliferative response to PHA in patients with LC. This suppressor effect is partially mediated by the prostaglandins released by the monocytes.