Transforming growth factor-alpha (TGF alpha) is a cytokine secreted by stimulated alveolar macrophages (AM) in vitro and after in vivo particulate or hyperoxia exposure and has been implicated in the processes of postnatal lung development. It is unknown if AM TGF alpha secretion changes during normal postnatal lung development. After sacrifice of New Zealand white rabbits on postnatal d 0-2, 5-7, 9-10, 14, 21, and 28 and > 4 mo (adult), AM were isolated by discontinuous density centrifugation and placed in culture in the presence or absence of concanavalin A (ConA) for 24 h. Media were collected, and the concentration and isoforms of TGF alpha in AM media samples were determined by an epidermal growth factor/TGF alpha radioreceptor assay and Western immunodetection, respectively. TGF alpha was present in media of AM from the 1.06 and 1.08 g/dL Percoll densities, but not in the 1.10 g/dL density. Statistically significant differences in TGF alpha secretion by unstimulated and ConA-stimulated AM at the various ages were not detected until d 14 (p < 0.02). Western blot analysis of unstimulated AM media samples from d 0-7 rabbits demonstrated the presence of TGF alpha isoforms at 46, 30, and 14.3 kD. At later postnatal ages (> or = d 9), a single 14.3-kD isoform was present. In contrast, analysis of ConA-stimulated AM media samples showed TGF alpha isoforms at 46, 30, and 14.3 kD for all ages; however, the 6-kD mature isoform was present only in juvenile (d 28) and adult media.(ABSTRACT TRUNCATED AT 250 WORDS)