Application of cyclic mechanical strain to vascular smooth muscle (VSM) cells elicits distinct cellular responses depending on extracellular matrix composition. We now examine activation of p42/p44 MAP kinase (ERK) and c-jun amino terminal kinase (JNK/SAPK) by cyclic (1 Hz) mechanical strain in neonatal rat VSM cells cultured on pronectin or laminin. In cells grown on pronectin, mechanical strain activated both ERKs (peak 10-30 min) and JNK/SAPK (peak 15-30 min). On laminin, mechanical strain induced a comparable activation of JNK/SAPK to that seen on pronectin, but no significant activation of ERKs. In contrast, application of strain to adult VSM cells activated both enzymes independently of extracellular matrix composition. In neonatal VSM cells, cyclic strain induced SM-1 smooth muscle myosin in cells cultured on laminin, but not on pronectin.. Thus in neonatal VSM cells, activation of ERKs and induction of SM-1 myosin by mechanical strain depend on extracellular matrix composition.