The synthesis of different diazonium salts derived from homo- and heterocyclic aromatic amines bearing anionic residues is described. The chemical stabilities of these compounds were established at different pH's, and the compounds were tested accordingly in binding experiments for the rat brain gamma-aminobutyric acid (GABA) receptor, for which they could ultimately be used as irreversible affinity or photoaffinity probes. The aromatic heterocyclic series studied were 2-aminoimidazole, 2-aminothiazole, and 4-aminopyridine N-oxide. The derived diazonium salts are unstable compounds at neutral pH unless they are able to be deprotonated to the corresponding diazo form. As such, the 2-diazoimidazole-4(5)-acetic acid (3b) is stable in neutral medium and recognizes the GABA receptor (IC50 = 70 microM). The homocyclic aromatic diazonium salts showed sufficient stability to be tested in binding experiments. The diazonium salts derived from m-sulfanilic acid and 8-sulfonaphthylamine were the most interesting (10b, IC50 = 10 microM; 15b, IC50 less than 100 microM). In this series, the compounds that deprotonate at neutral pH (hydroxybenzenediazonium derivatives 12b-14b) showed increased chemical stability but decreased affinity for the GABA receptor. This difference between the diazoimidazole and the diazohydroxybenzene series is attributed to a different charge distribution between the two series. The ligands 3b, 10b, and 15b can be used as potential irreversible probes for the GABA receptor.