The present results further confirm the usefulness of the push-pull cannula to study the in vivo activity of several neural systems in conscious, freely moving animals. However, it is evident that the inflammatory reaction to the local injury induced by the cannula may have different consequences in the function of a particular brain area. In the caudate nucleus, the responsiveness of the dopaminergic terminals of the nigrostriatal DA system to local infusion of AMPH was clearly reduced after the first two to three weeks post cannula implant. In contrast, in the hypothalamus of the rat and the rabbit, the spontaneous fluctuating activity of the LHRH pulse generator remained unaffected during a two to three month period when several perfusions could be performed in the same animal. Further studies will be required to establish the reasons for such marked differences in response to injury of these two brain structures. Various neurochemicals can be measured simultaneously from the hypothalamus of conscious rabbits. The present results indicate that NE hypothalamic impulse flow increases during the afternoon whereas the impulse flow of DA (as estimated by DOPAC output) decreases or does not change. In rabbit No. 2, simultaneous measurement of hypothalamic NE release and LHRH release indicates an absence of correlation. In sharp contrast, the simultaneous measurement of prostaglandin E2 release and LHRH release from the hypothalamus of rabbit 2-ER revealed a closer association between these two neuronal events. Apparently the push-pull technique can be used to examine long-term seasonal as well as circadian (extended 24 hr perfusion) spontaneous changes in the activity of the LHRH pulse generator in individual animals. It seems that seasonal changes characterize the function of the rabbit LHRH pulse generator. Lastly, physiological doses of progesterone infused for short times directly into the hypothalamus of female rabbit stimulate the LHRH pulse generator of this species with marked increases in the amplitude of the LHRH signal. In conclusion, the PPP technique coupled to HPLC-EC and RIA procedures to measure localized release of neurotransmitters, metabolites, and neuropeptides simultaneously in the same perfusate samples from discrete brain areas appears to be a powerful technique in furthering our knowledge of the in vivo local neurochemistry of the brain of conscious, freely moving animals.