Intravital microscopy of the hamster cheek pouch was adopted to serve as a model for quantitative studies of microvascular dynamics and parallel measurements of histamine release during immediate-type mast cell-dependent reactions. Topical challenge with specific antigen in the cheek pouch of immunized hamsters caused an acute inflammatory reaction, including leakage of plasma, vasodilation, and accumulation of leukocytes. Several lines of evidence indicated that the response was due to activation of mast cells: 1) an almost identical inflammatory reaction was seen after challenge with the mast cell secretagogue compound 48/80; 2) both antigen and compound 48/80 evoked distinct mast cell degranulatio and histamine release; 3) blockage of histamine 1-receptors reduced the plasma leakage response (but not leukocyte accumulation) to antigen and compound 48/80 in a very similar manner. In addition, fluorescein-labelled antigen bound specifically to mast cells in cheek pouches of immunized animals, suggesting involvement of mast cell-fixed antigen-specific antibodies, possibly immunoglobulin E. It is suggested that vasodilating prostaglandins exert both pro- and anti-inflammatory actions in vivo, and that they modulate acute allergic inflammation by i) inhibition of inflammatory mediator release, most likely unrelated to prostanoid-induced vasodilation, but caused by cAMP elevation in the mediator-secreting cells, and ii) enhancement of the target action of individual inflammatory mediators (i.e. plasma leakage and leukocyte emigration), most likely as a direct consequence of prostaglandin-induced vasodilation. This view is based on the following observations in the hamster cheek pouch: 1) Inhibition of prostaglandin synthesis with two different nonsteroidal anti-inflammatory drugs (NSAIDs) greatly potentiated plasma leakage, leukocyte emigration and histamine release after challenge with antigen or compound 48/80. The enhanced antigen-induced extravasation of plasma and leukocytes was significantly reduced by 5-lipoxygenase inhibitors, but was unaffected by PAF-receptor antagonism. 2) All aspects of NSAID-induced potentiation, including the increased histamine release, were effectively prevented by topically applied prostaglandin E2 (PGE2, 30 nM), which per se caused a five-fold increase in arteriolar blood flow. Moreover, PGE2 as well as prostaglandin I2 (PGI2) in vasodilating concentrations suppressed the antigen-induced plasma leakage also in the absence of NSAID treatment. 3) In contrast to the mast cell-dependent reactions, the inflammatory effects of individual mediators histamine, leukotrienes B4 and C4) were not influenced by NSAID treatment, and were markedly enhanced by both PGE2 and PGI2.(ABSTRACT TRUNCATED AT 400 WORDS)