The antihyperlipoproteinemic agent acifran (AY-25,712) was administered double-blind to 14 Type IIa hyperlipoproteinemic patients for 12 weeks in dosages of 100 mg t.i.d. or 300 mg t.i.d. An additional seven patients received placebo. Fasting plasma lipid and lipoprotein concentrations were determined at baseline (mean of 3 values), Week 8 (mean of 6- and 8-Week values), and Week 12 (mean of 10- and 12-Week values). At Week 8, patients receiving acifran 100 mg t.i.d. showed low-density lipoprotein (LDL) cholesterol levels which were 13% lower than pretreatment baseline (p less than 0.01) and 14% lower than patients given placebo (p less than 0.05); high-density lipoprotein (HDL) cholesterol levels were 11% higher compared with either baseline or the placebo group (p less than 0.05); the LDL/HDL ratio was 20% lower than baseline (p less than 0.001) and 21% lower than the placebo group (p less than 0.05); total cholesterol was 8% lower than that of the placebo group (p less than 0.05). There was no apparent relationship between changes in plasma lipid concentrations and acifran dose or treatment duration except for triglycerides, which at Week 12 were 25% lower than baseline (p less than 0.001) and 35% lower than the placebo group (p less than 0.05) only in the acifran 300 mg t.i.d. group, in which HDL-cholesterol was concurrently 18% higher compared with placebo (p less than 0.05). In this 12-week study acifran provided safe and effective treatment for Type IIa hyperlipoproteinemia.