Adults with chronic granulomatous disease of childhood (CGD) have been described who remain relatively free of infection despite markedly abnormal neutrophil function. Monocyte function in four adults with this mild or atypical CGD syndrome was examined and compared to that of normal controls and to that of two patients with the more severe or classic CGD syndrome. Monocytes from patients with atypical CGD killed 75.7% +/- 2.6% (mean +/- SEM) of ingested organisms at 30 min, while monocytes from the patients with classic CGD killed only 50.3% +/- 4.2% of bacteria (p less than 0.001). The difference in bactericidal activity between atypical CGD monocytes and normal monocytes was relatively small (75.7% +/- 2.6% versus 88.1% +/- 3.7%, respectively) but was statistically significant (p = 0.007). Monocytes from both atypical and classic CGD patients showed markedly impaired oxidative metabolism. Differences in monocyte bactericidal activity may explain why atypical CGD patients have fewer infections than classic CGD patients. The presence of nonoxidative bactericidal mechanisms in atypical CGD monocytes is suggested by the demonstration of bactericidal activity despite severe oxidative metabolic defects.