1. The ability of 1,3,8-substituted xanthines to antagonize the inhibitory effects of adenosine receptor agonist on the amplitude of nerve-evoked twitches of the rat phrenic-diaphragm and on the amplitude of orthodromically-evoked population spikes, recorded from the CA1 pyramidal cells of rat hippocampal slices, was investigated. 2. 1,3-Dipropyl-8-cyclopenthylxanthine (DPCPX), 1,3-dipropyl-8-(carboxymethyloxyphenyl)xanthine (XCC), 1,3-dipropyl-8-(4-[2-aminoethyl)amino)carbonylmethyloxyphenyl)x ant hine (XAC), 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX), 8-phenyltheophylline (8-PT), 1,3-diethyl-8-phenylxanthine (DPX) and PD 115,199, in concentrations virtually devoid of effect on neuromuscular transmission, shifted to the right in a near parallel manner the log concentration-response curve for the inhibitory effect of 2-chloroadenosine (CADO) on nerve-evoked twitches of the phrenic-diaphragm. Linear Schild plots with slopes near to unity were obtained for all the xanthines. 3. The order of potency of the xanthines as antagonists of the effect of CADO in the phrenic-diaphragm was DPCPX (Ki = 0.54 nM) greater than XCC (Ki = 10 nM), XAC (Ki = 11 nM), PACPX (Ki = 13 nM) greater than DPX (Ki = 22 nM), 8-PT (Ki = 25 nM) greater than PD 115,199 (Ki = 57 nM). The potency of DPCPX in antagonizing the inhibitory effects of R-N6-phenylisopropyladenosine (R-PIA) and 5'-N-ethylcarboxamide adenosine (NECA) on nerve-evoked twitch response was not statistically different from its potency in antagonizing the inhibitory effect on CADO. 4. In the hippocampal slices, DPCPX, XCC and XAC, used in concentrations virtually devoid of effect on population spike amplitude, shifted to the right in a near parallel manner the log concentrationresponse curve for the inhibitory effect of CADO on the amplitude of the population spikes. The Schild plots were linear with slopes near unity. 5. The potencies of DPCPX (K, = 0.45 nM) and XAC (K, = 11 nM) in antagonizing the inhibitory adenosine receptor at the hippocampus were similar to their potencies for antagonism of the inhibitory adenosine receptor at the phrenic-diaphragm. XCC was only slightly more potent (K, = 5.4 nM) as an antagonist of the adenosine receptor in the hippocampus than in the phrenic-diaphragm. 6. The results suggest that the inhibitory adenosine receptors in the phrenic-diaphragm and in the hippocampus of the rat are similar, and that according to the antagonist potencies, these receptors belong to the A1-adenosine receptor subtype.