A pulmonary infection caused by both Toxoplasma gondii and cytomegalovirus (CMV) developed in a heart transplant recipient. A presumptive diagnosis of CMV pneumonitis was made on the basis of a skin biopsy finding demonstrating CMV inclusions. This diagnosis was later supported by a positive pleural fluid culture for CMV, a greater than fourfold increase in CMV IgG antibody, and a response to therapy with ganciclovir sodium. Biopsy of skin lesions in patients at risk for CMV infections may represent an important early diagnostic tool.