The recombinant alpha2-adrenoceptors, designated as alpha2a and alpha2d, have highly similar amino acid sequences, but distinct pharmacological properties. It has been suggested that these two receptor subtypes are species orthologs, since the alpha2-adrenoceptors of a given species have pharmacological characteristics corresponding to either the alpha2a- (human, pig) or alpha2d- (rat, mouse, guinea pig, cow) adrenoceptor. Radioligand binding assays in rabbit adipocyte suggest alpha2D-adrenoceptor pharmacology. However, functional studies examining prejunctional alpha2-adrenoceptors in several tissues pharmacologically define the receptor of the rabbit as an alpha2A-adrenoceptor rather than an alpha2D-adrenoceptor. We characterized the alpha2-adrenoceptor of rabbit adipocyte and platelet, comparing the ability of norepinephrine and 13 adrenoceptor antagonists to inhibit the binding of [3H]RX821002 with the affinity of these drugs for the human alpha2a-adrenoceptor or the rat alpha2d-adrenoceptor. Pharmacological characteristics of the adipocyte and platelet receptor were very similar, with an excellent correlation between pK(i) values (r2 = 0.95, slope of regression = 1.01). Drug affinities for both platelet and adipocyte receptors correlated better with the alpha2a-adrenoceptor (r2 = 0.68-0.77) than with the alpha2d-adrenoceptor (r2 = 0.37-0.38). Despite the relatively low affinity of the rabbit adipocyte alpha2-adrenoceptor for yohimbine and rauwolscine, this receptor, as well as the platelet receptor, have alpha2A-adrenoceptor pharmacology. Subtle differences in the alpha2-adrenoceptor binding characteristics of these native rabbit tissues compared with the recombinant human alpha2a-adrenoceptor may result either from minor differences in the sequence of human and rabbit alpha2a-adrenoceptors or from differences in the environment to which native and recombinant receptors are exposed.