Pneumocystis carinii (PC) is an exclusively extracellular pathogen which causes pneumonia in immunocompromised individuals, Histologic studies have demonstrated that PC organisms attach preferentially to type I alveolar epithelial cells and rarely bind to type II cells. Previous reports have demonstrated that cultured type II cells develop a type I cell-like phenotype and express type I cell surface antigens, The current study examines the attachment of PC organisms to isolated rat type II alveolar epithelial cells as a function of time in culture, PC attachment to isolated type II cells increased as the type II cells differentiated in culture from 2.3 +/- 1.2% on Day 2 to 18.4 +/- 2.7% by Day 8, Previous studies have indicated a role for fibronectin (Fn) and Fn receptors as mediators of PC attachment, Addition of anti-Fn antibodies decreased attachment of PC to Day 8 type II cells from 19.4 +/- 2.5% to 9.4 +/- 1.9% (P < 0.01), Addition of antibodies to the cy, and alpha(5) integrin subunits resulted in significant decreases in PC attachment to Day 8 type II cells, Examination of expression of alpha(v) and alpha(5) integrins on Day 2 and Day 8 type II cells demonstrated increased expression of both alpha(v) and alpha(5) integrin subunits on Day 8 type II cells, Overall these data indicate that attachment of PC to isolated rat type II cells increases as the cells differentiate into a type I cell-like phenotype in vitro and correlates with increased expression of Fn-binding integrins on the cell surface of the cultured type II cells. (C) 1995 Academic Press, Inc.