Atherosclerotic intimal smooth-muscle cells (SMCs) in vitro showed higher growth activity than did medial SMCs obtained from either atherosclerotic or normal aortas. Using an electron microscope, it was proved in primary cultures by an explant method that intimal SMCs had rich organelles and fewer filaments in their cytoplasms. They were regarded as synthetic phenotype. In contrast, most medial SMCs had rich filaments and fewer organelles. They were regarded as contractile phenotype. When atherosclerotic intimal and normal medial SMCs were plated on type I collagen gel, cytoplasmic cyclic adenosine monophosphate concentration increased and DNA synthesis was suppressed. Intimal SMCs cultured on the gel showed contractile phenotype. Dibutyryl cyclic adenosine monophosphate added to culture media decreased DNA synthesis and altered cellular phenotype to a contractile state. Intimal SMCs were more resistant to injury by hyperlipidemic low-density liproprotein and homocysteine. Lysosomal enzyme activity was enhanced in intimal SMCs.