Pseudohypoparathyroidism (PHP) is a hereditary disorder with typical dysmorphic signs and clinical and laboratory symptoms of hypoparathyroidism which is resistant however to parathyroid extract. ALBRIGHT and coworkers supposed that this resistance was caused by an inability of the renal tubules to respond to parathyroid hormone. On three children, suffering from PHP, we could demonstrate that parathyroid extract-resistance disappears during treatment with vitamin D. Measurements of urinary excretion of cAMP, the second messenger for parathyroid hormone, in the same patients showed low basal levels of this nucleotide, which could not be stimulated by parathyroid extract either before or during vitamin D-treatment. This constantly low and by parathyroid extract not stimulable cAMP-excretion is now the symptom with the most diagnostic value for PHP. Beyond this the finding of this defective urinary excretion of cAMP in PHP was able to explain the hitherto unknown pathogenesis of this disorder: the parathyroid hormone -- sensitive adenylcyclase system is here unable to mediate the action of parathyroid hormone on its target cells, so causing a peripheral block of parathyroid-hormone activity. Therefore GREENBERG and coworkers justly term PHP a disease of the second messenger.