The effects of the divalent cation ionophore A23187, upon microvascular permeability have been investigated in single perfused capillaries and venules in the mesenteries of pithed frogs. In all experiments, the vessels were perfused with Ringer solutions containing the macromolecules Ficoll 70 (40 mg ml-1) and bovine serum albumin (10 mg ml-1). Hydraulic permeability (Lp) of the vessel walls and the effective osmotic pressure (sigma delta pi) exerted across them by the perfusate macromolecules were estimated by the method of Michel (1980). In eleven experiments addition of A23187 to the perfusate raised Lp from a mean value (+/- S.E.M.) of 4.76 (+/- 1.05) x 10(-7) cm s-1 cmH2O-1 to one of 11.97 (+/- 1.96) x 10(-7) cm s-1 cmH2O-1 and reduced sigma delta pi from a mean (+/- S.E.M.) of 16.5 (+/- 2.01) cmH2O to one of 7.6 (+/- 1.93) cmH2O. The effects of A23187 on Lp and sigma delta pi were reversible. A23187 was found to increase Lp and reduce sigma delta pi after the mesentery had been exposed to compound 48/80 to degranulate the mast cells two or more hours previously. A23187 also appeared to be effective in raising Lp and lowering sigma delta pi in the absence of Ca2+ ions from the perfusate and superfusate. The ionophore was found to reduce permeability, however, when Mg2+ ions were removed from the perfusate and superfusate both in the absence and in the presence of Ca2+. This reduction in permeability could be converted into an increase in Lp and fall in sigma delta pi if Mg2+ were restored to the superfusate. It is concluded that A23187 increases vascular permeability in a reversible manner and that Mg2+ ions in the extracellular fluids are necessary for its action.