Pneumocystis carinii (PC) is a leading cause of pneumonia in immunocompromised patients. Previous work has shown that fibronectin (Fn) and Fn-binding integrins mediate PC attachment to lung cells in vitro. Gamma-interferon (gamma-IFN) is a major factor in host defence against PC infection. To determine the effect of gamma-IFN on PC attachment to lung cells, the alveolar epithelial cell line A549 was incubated with gamma-IFN (0-10(4) U mL(-1)) and attachment of 51Cr-labelled PC to the A549 cells was quantified. PC attachment was significantly decreased (P < 0.01) by addition of gamma-IFN with no evidence of injury to either the PC or A549 cells. Effects of gamma-IFN on PC attachment were observed after 24 h and reached a maximum after 48 h of incubation. To investigate the mechanism of this decrease, we examined integrin expression on gamma-IFN-treated A549 cells. A549 cell expression of the alpha5 and beta1 integrin subunits was decreased, whereas expression of the alpha(v) subunit was unchanged. Northern blot analysis showed a similar decrease in mRNA for the alpha5 and beta1 integrins. Therefore, gamma-IFN-mediated inhibition of PC infection may, in part, result from inhibition of PC attachment to alveolar epithelial cells caused by gamma-IFN-induced decreases in alveolar integrin expression.