The relationship between functional residual capacity (FRC) and shunt development with halothane anesthesia in 18 nonobese surgical patients (age, 21-34 yr) was studied. FRC was measured by helium dilution, and intrapulmonary shunt was distinguished from ventilation-perfusion inequality by multiple tracer inert gas elimination analysis. Awake supine FRC was 34.6 +/- 6.6% (mean +/- SD) of total lung capacity (TLC), and closing capacity (CC) was 29.8 +/- 5.3% of TLC. Anesthesia, muscle paralysis, tracheal intubation, and mechanical ventilation produced an average 14.6 +/- 13.3% FRC reduction to an average anesthesia FRC 29.8% of TLC (P = 0.002). Shunt increased from 1.2% +/- 1.5% awake to 8.6 +/- 8.3% during anesthesia (P = 0.005). A nonlinear relationship was found between shunt and FRC/TLC so that anesthetized subjects with an FRC less than awake CC had an average 11.4 +/- 8.3% shunt, whereas subjects with an FRC greater than CC had a 2.4 +/- 2.8% shunt (P = 0.025). Nonsmokers developed shunt only if FRC was less than CC. Smokers showed a significantly higher shunt for a given (FRC-CC)/TLC compared to nonsmokers (P less than 0.001). The slope of the regression of shunt on BMI (body mass index = weight/height2) showed a significant increase during anesthesia (P = 0.005), and smokers had a significantly higher slope compared to nonsmokers (P = 0.001). These findings suggest a gravity-dependent mechanism for intrapulmonary shunting during anesthesia. Therefore, shunting was due to dependent regional lung volume reduction associated with an FRC decrease to less than closing capacity. The enhanced intrapulmonary shunting in smokers may have been related to the increased dependent regional residual volume associated with smoking.