These experiments combined electrophysiological recordings from hippocampal slices with application of drugs to and sampling of extracellular fluid from a restricted region of the slice using a push-pull cannula placed under the slice in an interface chamber. Stable and apparently normal extracellular and intracellular recordings could be obtained directly over the tip of the cannula and solutions changed without disturbing the recording. Relatively rapid effects (1-5 min) were observed when TTX, CNQX, or medium containing 50 mM K+ were applied via the cannula and recovery from these effects was achieved. In addition, effects were restricted to the immediate vicinity of the cannula; neurones recorded several hundred micrometers away were apparently unaffected. Samples of extracellular fluid obtained as minute fractions during the application of high K+ containing medium contained higher concentrations of GABA, aspartate and glutamate than control fractions but the same levels of other amino acids, e.g., isoleucine and leucine. With appropriate design of push-pull cannula and recording chamber, therefore, stable electrophysiological recordings can be combined with localized extracellular fluid sampling and rapid and localized application of test solutions in an interface slice chamber.