The aim of this work was to determine whether the effects of weight loss on coronary heart disease (CHD) risk factors are comparable in men and women and whether the long term impact of modest weight loss is as great as the initial response. Changes in CHD risk factors were examined at 6 month intervals in 159 moderately overweight subjects who were participating in an 18 month behavioral weight loss program. Men experienced greater decreases in blood pressure, triglycerides, and waist-to-hip ratio (WHR) and greater increases in HDL-cholesterol with weight loss than women. Most of these gender differences were removed by adjusting for baseline values and changes in BMI. After these adjustments, improvements in WHR at 18 months were shown to be greater in women than in men. Participants (n= 39) who lost 4.5 kg or more from baseline to 6 months (mean weight loss of 11.8 kg or 13% of initial body weight) and maintained this weight loss within+/-2.3 kg had significant long term improvements (through 18 months) in triglycerides, HDL and LDL-cholesterol, WHR, systolic and diastolic blood pressure, and fasting and 2 h insulin. Changes in HDL-cholesterol, the HDL: Total cholesterol ratio, and WHR actually increased between 6 and 18 months and improvements in all other parameters were maintained over time. Men have greater improvements in CHD risk factors with weight loss than women, but this gender difference appears to derive from differences in CHD risk factors at baseline and differences in weight loss.(ABSTRACT TRUNCATED AT 250 WORDS)