Polymorphonuclear leukocytes (PMN) are recruited to the lungs to defend against injury and infection. However, PMN undergo apoptosis, thereby losing functional ability within hours, and die with lysis soon thereafter unless they receive specific signals preventing this phenomenon. We hypothesized that alveolar macrophages (AM) could provide these signals. Therefore AM, obtained through bronchoalveolar lavage of healthy volunteers (n = 9), were cultured for 24 h, after which the AM conditioned media (AM-CM) were removed. Freshly isolated PMN, which showed no apoptosis, were suspended in AM-CM, as well as in unconditioned media (UM), and followed over 48 h for apoptosis and survival. In eight of nine patients, AM-CM contained tumor necrosis factor (TNF), which modestly delayed AM apoptosis so that the percentage of PMN apoptotic at 24 h was 77 +/- 6% in AM-CM compared with 91 +/- 2% in UM (P < 0.05). In one patient, urticaria developed early in the lavage, and this subject's AM-CM profoundly prevented apoptosis of PMN (to 10% at 24 h). PMN survival in this patient was similarly enhanced, so that at 48 h of culture it was 60%, compared with 45 +/- 8% in AM-CM and 30 +/- 6% in UM (P < 0.05 UM vs. AM-CM). Granulocyte/macrophage colony-stimulating factor (GM-CSF), in addition to TNF-alpha, partly accounted for this medium's activity. Thus AM can delay apoptosis in PMN through production of TNF-alpha and in some cases by GM-CSF. When activated in vivo by conditions such as an allergic reaction, AM can rapidly and profoundly suppress PMN apoptosis.