Alveolar macrophages (AM), harvested from the lungs of untreated normal young rabbits (New Zealand White) 14 days to 8 weeks of age, exhibited a state of migration stimulation compared to AM from normal adult rabbits (5 to 6 months of age). Migration of AM from normal adult rabbits (New Zealand White) was stimulated 2.0- to 2.5-fold when incubated with sera from 39- to 46-day-old rabbits compared with sera from normal adult rabbits. Furthermore, 4-day spleen cultures obtained from animals 28 to 59 days of age yielded supernatants that also stimulated the migration of adult AM. The spleen cell culture supernatants from 42- to 49-day-old animals had the greatest activity and stimulated the migration of adult AM 2.5- to 3.2-fold compared to the supernatants from adult normal rabbits. The peak production of migration enhancement factor (MEF) by splenic lymphoid cells coincided with the peak activities found in the sera. It was observed that nonadherent peanut agglutinable lymphoid cells produced MEF. When sera or culture supernatants containing MEF were mixed with MIF-containing adult sera or spleen cell culture supernatants, the respective activities were neutralized. The large migrations of normal neonatal AM were diminished by the addition of MIF-containing sera obtained from BCG-sensitized/challenged rabbits. In contrast, AM from BCG-sensitized rabbits, which exhibited a state of reduced migration, were enhanced by MEF-containing sera from untreated young rabbits. Three peaks of MEF activity were detected in Sephadex G-100 column fractionated sera from 42-day-old rabbits having MWs of approximately (Peak I) 80,000, (Peak II) 43,000, and (Peak III) 8000 to 18,000; most of the activity was found in peaks II and III. Two peaks of MEF activity were detected in Sephadex G-100 column-fractionated spleen cell culture supernatants from 42-day-old rabbits having MWs of approximately (Peak I) 35,000 to 43,000 and (Peak II) 10,000 to 14,000; most of the activity was in peak I which corresponds to peak II of the serum fractionation experiment. Collectively, these data indicate that MEF is a lymphokine that could be important in the modulation of cell-mediated immune effector responses.