Summary: Several methyl 17ß-carboxyester derivatives of natural and fluorinated glucocorticoids were synthesized in order to compare their potency to compete for [ 3 H]dexamethasone binding sites in human spieen tumour cytosols (äs a source of large quantities of white blood cells) with their potency to inhibit phytohaemagglutinin-induced blastogenesis of normal human peripheral lymphocytes. The 17ß-carboxylic acids neither show binding activity nor Inhibition of blastogenesis. Methylation partially restores the binding capacity and the intensity of this effect depends on the kind of ring substitütions. The sequence of binding potency is identical compared to that of parent steroids and was found to be in the following order: desoximetasone > dexamethasone > corticosterone > Cortisol > progesterone > 17-hydroxyprogesterone. The phytohaemagglutinin-induced Stimulation of [ 3 H]thymidine incorporation resembles the order of binding potency. The methyl 17ß-carboxyester derivatives of progesterone, 17-hydroxyprogesterone and betamethasone are inactive. The N-benzyl 17ß-carboxamide analogs of dexamethasone and betamethasone behave like their corresponding carboxyesters, suggesting an important influence of the side chain conformation of 17ß-carboxyl derivatives on glucocorticpid receptor binding.