The influences of cell membrane permeabilization (skinning) on the okadaic acid-induced inhibition of vascular smooth muscle contraction were studied in guinea pig hepatic portal vein. Pretreatment by 1 microM okadaic acid in the absence of Ca(2+) suppressed subsequent submaximal Ca(2+)-induced contraction in preparations permeabilized with Staphylococcus aureus alpha-toxin or beta-escin, but not in those treated with saponin or Triton X-100. The SDS-PAGE of elutants from the preparation suggests that the loss of the inhibitory effect of okadaic acid in preparations skinned with saponin or Triton X-100 results from the leakage of some cellular components with a molecular mass of 67 to 200 kDa.