Twelve healthy male volunteers received single market‐image 40‐mg oral doses of lovastatin and simvastatin (both lactone prodrugs), or pravastatin (α β‐hydroxyacid) at 1 week intervals in a three‐way crossover study to quantify HMG‐CoA reductase inhibitors in plasma. Multiple plasma samples were collected up to 24 hours after the dose and assayed for active and total HMG‐CoA reductase inhibitors. After equal oral doses, higher plasma concentrations of HMG‐CoA reductase inhibitory activity after pravastatin than after either lovastatin of simvastatin (2–3 fold greater area under the concentration‐time curve) suggest a greater potential availability of pravastatin‐related inhibitory activity to peripheral tissues.