Hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors are potent cholesterol reducing agents that have been successfully used for the treatment of heterozygous familial hypercholesterolaemia (FH). A recent investigation revealed that several constitutional and genetic factors significantly determined the response of plasma lipids and lipoproteins to the HMG CoA reductase inhibitor fluvastatin. Gender has been identified through multivariate analysis as a major determinant of the plasma high density lipoprotein (HDL) cholesterol response. The current analysis was undertaken to determine possible gender-related fluvastatin dose-response differences. The analysis revealed that for HDL cholesterol, gender-related differences reach statistical significance only at the highest fluvastatin dose of 40 mg/day (females 22.9%, males 12.9%, p < 0.01). In parallel, the change in low density lipoprotein (LDL) cholesterol: HDL cholesterol ratio, an indicator of ischaemic heart disease risk, was also found to be affected by gender (females -38.4%, males -32.2%, p < 0.01). For LDL cholesterol, no consistent gender-related differences were found. In conclusion, the response of plasma lipid levels to fluvastatin in heterozygote FH patients is significantly affected by gender, with females achieving a more marked overall response, as indicated by higher HDL cholesterol levels and a lower LDL cholesterol: HDL cholesterol ratio.