Abstract:The effect of pentylenetetrazol (Metrazol) on serum cholesterol concentration was studied in 29 patients with initial cholesterol levels of 200 mg per 100 ml or higher. In addition, placebo was administered to 10 suitably matched controls. The dosage of pentylenetetrazol was 200 mg four times daily.In the patients to whom the drug was continuously administered for four weeks, there was a statistically significant fall in the concentration of serum cholesterol at the end of two weeks, but a return to the initial high level at the end of four weeks. In the patients to whom the drug was intermittently administered (for two two‐week periods with a one‐week interval), there was a significant decrease in the concentration of serum cholesterol at the end of each two‐week period. In all cases there were no deleterious effects. The maximal hypocholesterolemic effect of pentylenetetrazol was at the end of two weeks, but this lowering effect disappeared when drug administration was continued.The study shows marked individual variations in the cholesterol‐lowering response of patients to pentylenetetrazol. Thus, with respect to the continuing search for such drugs, it would seem that no one drug will be effective in lowering blood cholesterol concentration in all patients. The type of hypercholesterolemia and the type of response to drug administration will each play i