Glycoprotein hormone alpha subunit (αSU) is expressed in nearly all thyreotroph adenomas and most gonadotrophinomas, but is less well documented in plurisecreting adenomas. We therefore examined the immunohistochemical (IHC) expression of αSU in a generally accepted model of plurisecreting adenomas (somatoprolactinic type) by comparison to a series of pure monosecreting somatotroph tumors. Fifty patients (32 females, 18 males) aged 15 to 68 years with clinical and/or biological acromegaly requiring adenomectomy were studied. Forty-five had clinical acromegaly and 5 had isolated amenorrhea and/or galactorrhea syndromes. Forty-eight of the 49 patients who had baseline assessments of plasma GH had a mean concentration of 5 ng/ml or more (normal value <5). Fifteen of the 46 patients who had baseline measurements of plasma PRL had a prolactinemia value greater than 20 ng/ml (normal value <20) but below 100 ng/ml, except for one patient. All the adenomas studied were positive by GH immunohistochemistry; 21 were immunostained by an antiPRL antibody and formed the “somatoprolactinic” (GH-PRL) group. Five of these 21 patients were male. The 12 female patients younger than 50 years had amenorrhea or galactorrhea, and one male patient complained of impotence. Eleven patients (9 females, 2 males) in this GH-PRL group had hyperprolactinemia. Sixteen of these GH-PRL adenomas were immunolabeled by aSU antiserum. The remaining 29 adenomas, which were immunonegative with the PRL antibody and formed the “somatotroph adenoma” (GH) group, were more frequent in male patients (13/29; 45%) compared to GH-PRL group. Eight amenorrhea or galactorrhea syndromes occurred among the 14 women younger than 50 years, 3 of whom had hyperprolactinemia. Thirteen of these 29 adenomas (45%) were immunopositive with αSU antibody. Compared to the GH group, the GH-PRL group had a significant higher frequency of amenorrhea and/or galactorrhea syndromes among women under 50 years (100% vs 57%; p<0.01), as well as hyperprolactinemia (55% vs 15%; p<0.01) and positive aSU immunoreactivity (76% vs 45%; p<0.05). The frequency of extrasellar macroadenomas was not different according to PRL or αSU immunoreactivity. Thus, in this series of somatoprolactinic adenomas, αSU immunopositivity was slightly more frequent than in a control group of pure somatotroph adenomas. Moreover, hyperprolactinemia was more frequent in patients with GH-PRL adenomas, although the size of the pure and mixed adenomas was not different. These results suggest that hyperprolactinemia and/or αSU immunopositivity are more often associated with mixed GH-PRL adenomas.