Bihormonal or plurihormonal pituitary tumors produce two or more hormones different in chemical composition, immunoreactivity, and clinical significance. Immunohistochemical and electron microscopic investigations and more recently molecular-genetic studies have provided conclusive evidence of the production of multiple hormones by pituitary adenomas. Most frequently, they produce GH, PRL, TSH, and/or alpha-subunit of the glycoprotein hormones. Other uncommon combinations may also be apparent. We report the case of a 40-yr-old acromegalic man with a pituitary macroadenoma. The pituitary tumor was removed by transsphenoidal surgery. Histological, immunohistochemical, electron microscopic, and immunoelectron microscopic examinations revealed that the tumor contains multiple hormones (GH, LH, and alpha subunit) and transcription factors. The application of different reagents yielded different patterns of positivity indicating that the validity of some common immunohistochemical reagents must be re-evaluated.