This familial hereditary condition is characterized by the association of Albright's osteodystrophy, resistance to parathormone (PTH) and a negative PTH test both for urinary phosphorus and cyclic AMP. The condition is caused by an anomalous alpha sub-unit of protein G, impairing its function. The result is defective transmembrane transduction of the PTH mediated signal. Protein G, coupled with all heptahelical membrane-spanning receptors, is ubiquitous, explaining the association of multiple hormone and neurosensory resistances. Resistance of the thyrotrope and gonadotrope axes should be explored to institute appropriate replacement therapy. TYPE IC: This type associates all the clinical and biological features of type Ia pseudohypoparathyroidism but without any protein G defect, suggesting another effector of signal transduction, perhaps adenylate cyclase, is involved. PSEUDOPSEUDOHYPOPARATHYROIDISM: Often in families with type Ia pseudohypoparathyroidism, subjects with Albright's osteodystrophy alone, with no features of PTH resistance, are said to have pseudopseudohypoparathyroidism. Protein G defects are also demonstrated in these subjects, confirming the relationship with type la pseudohypoparathyroidism and explaining the possible multiple hormone resistances observed. The phenotypic variability between type Ia pseudohypoparathyroidism and pseudopseudohypoparathyroidism would be related to genomic imprinting mechanism.