A new technique which combines skin microinjection of minute amounts of drugs (0.5 microliter) and measurement of capillary permeability by intravital fluorescence videomicroscopy and densitometry is introduced. Glass micropipettes with a tip diameter of 7-9 microns are inserted by a micromanipulator into the stratum papillare containing the capillary loops and used for microinjection by microsyringe and special dispenser. Transcapillary diffusion of sodium fluorescein applied by intravenous bolus injection is visualised by fluorescence videomicroscopy and stored on videotape. Perivascular fluorescent light intensity (FLI) is measured in arbitrary units (AU) by videodensitometry around the site of microinjection during playback of the videotapes. The method was tested by microinjection of 0.5 microliter histamine (1% solution) at the distal tibial plateau. Mean FLI values representing microvascular permeability were 2186 AU 10 min after microinjection of histamine, 420 AU after physiologic saline and 1228 AU after histamine combined with oral intake of 20 mg cetirizine. Cetirizine significantly reduced (P < 0.01) the increased permeability induced by histamine. However, the mean values after injection of the H1-blocker were still significantly enhanced (P < 0.01) when compared to the mean values observed after injection of physiologic saline solution, which provoked only minor microtrauma. The technique offers new scope for pharmacological testing in man.