Human chorionic gonadotropin (hCG) and hCG-like substance (hCG') in tissues and body fluids of normal subjects and patients with neoplasms were investigated for their physico-chemical and immunological and biological properties. A. HCG. (1) Derangement of hCG secretion in terminal choriocarcinoma patients was revealaed by marked heterogeneity of hCG and hCGAlpha subunit. (2) Radioimmunoassays of 748 serum samples from 139 patients under treatment for gestational trophoblastic neoplasms showed no general trend towards high hCGAlpha levels, a proposed indicator of disease recurrence. (3) A simple procedure for collection, concentration, and assay of urinary hCG was designed and applied successfully in a larger scale study on the detection of fetal loss in early pregnancy. (4) Chemically deglycosylated hCG was shown to have increased binding affinity for both LH and FSH receptors in granulosa cells, and to antagonize hCG-stimulated progesterone production during the early appearance of LH receptors in the cell. B. HCG-like substance. HCG' secreted during the late luteal phase of normal women with and without an intrauterine device as a contraceptive measure was found to be biologically active in a Leydig cell testosterone assay. In contrast, the episodically secreted hCG' after scheduled withdrawing of steroid contraceptives was biologically inactive and appeared to be mostly an hCGBeta-like subunit. These and our previous findings suggest that steroid hormones may modulate pituitary hCG' secretion in both quantity and quality.