We have recently established that canine narcolepsy (an autosomal recessive genetic model of the human disorder) is dramatically improved by treatment with α 2 antagonists such as yohimbine (Nishino et al: J Pharmacol Exp Ther 253:1145–1152, 1990). To further investigate the role of α 2 adrenoceptors in narcolepsy, receptors labeled with [ 3H] yohimbine were examined on platelets from human and canine narcoleptic subjects. Twenty-eight Doberman pinschers were studied, 7 controls (C), 7 heterozygous (Hz), and 14 narcoleptics (N) (age and sex matched), including eight animals born in a backcross setting (narcoleptic × heterozygous; 5 narcoleptics and 3 heterozygous). The K d and B max of each group respectively, were as follows: C, K d = 2.86 ± 0.76 nmoll L, B max = 295.78 ± 31.89 fmol/ mg protein; Hz, K d = ± 0.23 mol/ L, B max = 307.02 ± 22.21 fmol/ mg protein; and N, K d = 2.72 ± 0.45 nmol/ L, B max = 267.52 ± 19.47 fmol/ mg protein. No statistical differences were ound between groups using nonparametric (Kruskall-Wallis) statistical procedures, and there were no correlations between any binding parameter and symptom severity within the narcoleptic group. Platelet α 2 receptor affinity and density also did not differ between narcoleptic and heterozygous dogs in the backcross litter ( N [n = 5], K d = 1.94 ± 0.59 nmol/ L, B max = 290.6 ± 64.7 fmol/ mg protein; Hz [n = 3], K d = 2.83 ± 0.47 nmol/ L, B max = 294.2 ± 42.9 fmol/ mg protein). Fourteen human subjects, seven control and seven narcoleptics patients )age and sex mached), were included in the study. Narcoleptic subjects had excessive daytime sleepiness documented polygraphically and cataplexy. K d and B max values for control and narcoleptic patients were no different and were, respectively, K d = 1.38 ± 0.45 nmol/ L, B max = 275.37 fmol/ mg protein and K d = 1.49 ± 0.45 nmol/ L, B max = 268.69 ± fmol/ mg protein. Results indicate that narcolepsy is not associated with any change in platelet α 2 receptors as determined with [ 3H] yohimbine, in contrast with other neuropsychiatric with rapid-eye-movement sleep abnormalities such as depression.