The newly discovered imidazoline receptors have been found to be upregulated in patients with major depression (platelet 45 kDa and 35 kDa proteins) and in suicide victims (brain 45 kDa protein). The signalling pathways coupled to these receptors are not known however. The aim of this study was to quantify, in platelets of depressed patients, the density of various G proteins to assess possible associations with the abundance of imidazoline proteins. There were positive correlations between the immunoreactivities of 45 kDa imidazoline receptors and those of G alpha q/11 (r = 0.64, n = 19, p < 0.005), G alpha i2 (r = 0.46, n = 22, p < 0.05) and G beta (r = 0.62, n = 18, p < 0.01) proteins. The relationship with regulatory G alpha q/11 proteins suggests that this 45 kDa protein (putative I1 imidazoline receptor) may couple to phosphoinositide pathway in platelets. This finding might be of relevance in understanding the functional implications of the abnormal higher expression of imidazoline receptors (45 kDa protein) in the pathogenesis of major depression.