Two retrovirus-associated pulmonary diseases of sheep [ovine pulmonary carcinoma (OPC); sheep pulmonary adenomatosis], a bronchoalveolar carcinoma, and lymphoid interstitial pneumonia (LIP) were induced simultaneously in 9 of 9 neonatal lambs. The lambs were killed 8-28 weeks after intratracheal injection of lung tumor homogenate or lung fluid derived from sheep with naturally occurring OPC and ovine lentivirus (OvLV) infection. The inoculated lambs developed multifocal neoplasms of alveolar type II cells or nonciliated bronchiolar epithelial cells, LIP, and pulmonary lymph node hyperplasia, and all produced antibody to OvLV. OvLV was isolated from 6 of 7 lambs tested, and infectious center assay of pulmonary lavage cells from 3 lambs revealed that approximately 1 in 1,000 pulmonary lavage cells contained infectious lentivirus. Neither contact control lambs nor control lambs that received ultrafiltered lung fluid developed evidence of either disease or of OvLV infection. Lung fluid or tumor tissue of lambs with OPC contained a 26,000-dalton protein that cross-reacted with antiserum to p27 to Mason-Pfizer monkey virus, a type D retrovirus. The fact that no antigenic cross-reaction between OvLV and type D retroviruses has been demonstrated supports the presence of two retroviruses in sheep with OPC. Although the contributions of each agents to oncogenesis in this model are difficult to evaluate, the rapid development of two retrovirus-induced pulmonary diseases in experimentally inoculated lambs suggests an etiologic or pathogenetic synergism between these two members of the family Retroviridae.