The numbers of alveolar macrophages (AM) are known to be low in utero and to increase rapidly after birth. This study analyzed factors related to the appearance of AM in the lungs of term and preterm monkeys (Macaca nemestrina). We found that the numbers of AM were greater at birth in term than in preterm monkeys (p less than 0.01) and that they increased with postnatal age in term animals (r = 0.86) and in preterm animals without hyaline membrane disease (HMD) (r = 0.79). In contrast, the numbers of AM did not increase with postnatal age in preterm animals with HMD (r = 0.17). By multivariant analysis, AM numbers correlated most strongly with a combination of 2 variables: lavage fluid phospholipid and absence of HMD (r = 0.996). Preparations of alveolar surface-active material from newborn monkeys and to a lesser degree from adult monkeys were found to stimulate migration and polarization of monkey AM and blood monocytes in vitro. The migration-stimulating factor(s) in alveolar surface-active material had an apparent molecular weight greater than 10,000 and appeared not to be a lipoxygenase product of arachidonic acid metabolism. These data indicate a correlation between factors regulating lung pressure-volume stability and AM numbers and are consistent with a potential role for components of alveolar surface-active material in regulating the perinatal increase in AM.