Human 5-hydroxytryptamine1B (5-HT1B; also designated 5-HT1D beta) receptors and 5-HT1D (also designated 5-HT1D alpha) receptors are distinct molecular entities which mediate serotonergic neurotransmission. The often confusing variability in nomenclature for these two G protein-coupled receptors derives from a preliminary observation that these receptors display nearly indistinguishable pharmacological properties. The present study analyzed a series of 21 drugs, 8 of which were found to be at least an order of magnitude more potent at 5-HT1D than 5-HT1B receptors. These data provide pharmacological evidence that human 5-HT1B and 5-HT1D receptors are distinct molecular entities which represent independent targets for future drug development. Furthermore, these data indicate that a number of selective pharmacological agents already exist and can be used to analyze the functional roles of 5-HT1B and 5-HT1D receptors.