Veterans are frequently older, have more chronic illnesses, and take more medications than subjects volunteering for clinical trials. Because these factors may impair the effectiveness of lipid-lowering drug therapy, the effectiveness of drug therapy in veterans may differ from that measured in randomized controlled trials. In 297 patients with type IIa hyperlipidemia attending a large Veterans Administration Medical Center lipid clinic, adverse effects, compliance, lipid and lipoprotein responses to drug therapy were prospectively monitored. Bile acid sequestrants (4 packets/day) were associated with a high rate of adverse effects, and had the highest drug discontinuance rate (37%) and poorest compliance (73 +/- 3% of the doses prescribed reported ingested) of all agents. Patients aged > 60 years tolerated therapy with bile acid sequestrants less well than did younger veterans (p < 0.01). Niacin (1.5 g/day) also had a high drug discontinuance rate (27%). Lovastatin (20 mg/day) had the lowest drug discontinuance rate (2%) and the highest compliance (90 +/- 2%). Lovastatin also reduced low-density lipoprotein (LDL) cholesterol the most (-21.6 +/- 2.0%), whereas niacin produced the largest increase in high-density lipoprotein (HDL) cholesterol (+/- 14.3 +/- 2.2%); both niacin and lovastatin produced similar reductions in the LDL/HDL ratio. However, psyllium (10.4 g/day) reduced LDL cholesterol by only 2%, and had no effect on the LDL/HDL ratio. Psyllium produced larger LDL cholesterol reductions in patients aged < 60 years than in older patients (p < 0.01). Niacin and lovastatin are effective drugs for hypercholesterolemia management in the Veterans Administration Medical Center setting.(ABSTRACT TRUNCATED AT 250 WORDS)