The relation between plasma lipids and gallbladder disease was examined by using data collected between 1984 and 1987 from 1,303 Rancho Bernardo, California, women aged 50 years and older. In univariate analyses and after adjustment for age and body mass index, high density lipoprotein cholesterol (HDL cholesterol) and low density lipoprotein cholesterol (LDL cholesterol) were inversely related and triglyceride level was positively related to gallbladder disease. However, using multiple logistic regression, only LDL cholesterol, triglycerides, age, and body mass index were significantly related to a history of gallbladder disease, whereas HDL cholesterol was no longer associated with gallbladder disease. The risk of gallbladder disease increased with greater age, body mass index, and triglyceride level, but decreased with increasing LDL cholesterol level. Total amount of alcohol consumed per week, number of cigarettes smoked per day, and current estrogen use were not significantly associated with gallbladder disease. The relation of HDL cholesterol and LDL cholesterol to the risk of gallbladder disease requires further investigation.