Granuloma formation studies were performed on lungs of guinea pigs sensitized with FCA over 2 to 17 months. Prolonged time of sensitization revealed more granulomatous pulmonary tissue. An intravenous booster of FCA in the animals that had been sensitized for 3 months yielded enhanced granuloma formation within 5 days. The histopathology of these lungs was comparable with that seen in lungs of animals after 17 months of sensitization without booster. Enhanced local proliferation of macrophages, measured by [3H]thymidine incorporation and autoradiography, was seen in the lungs of the animals that had received boosters. Moreover, 67Ga scintigraphy was strongly positive in these animals. Scintigraphy of cell suspensions of pulmonary tissue from these animals showed that 67Ga was predominantly taken up (quantitatively as well as qualitatively) by the alveolar macrophages. Cell suspensions of sarcoidosis patients, prepared in the same way, showed only a low level of 67Ga uptake, one comparable to that of the pulmonary cell suspensions of the sensitized animals that had not received boosters. It is suggested that a negative scintigraphy in patients with chronic pulmonary granulomatous disorders could be (partly) explained by the absence of activated macrophages.