The unbound fraction of propranolol was found to vary from 1.9 to 13.2% in 434 plasma samples from members of 132 families. As expected, there was a linear correlation between the ratio of bound/unbound propranolol and the orosomucoid concentration (r = 0.67, P less than 0.001). Albumin concentration did not influence propranolol binding. The unbound fraction was negatively correlated with obesity and alcohol intake, but was not significantly influenced by age and sex. By applying path analysis, 21% of the variability in propranolol binding could be ascribed to genetic factors and 5% to common environmental factors.