Many physiological processes in organisms are regulated by a relatively small number of steroid honnones. Androgens are the so-called male sex steroid hormones which control growth, differentiation and functions of male reproductive and accessory sex tissues. Androgens are mainly produced in the testis and circulate in the blood. They diffuse in and out of all cells, but are retained with high affinity and specificity in target cells by an intranuclear binding protein, termed the androgen receptor. Once bound by androgens, the androgen receptor undergoes a conformational change allowing the receptor to bind with high affinity to DNA and to modulate transcription of certain genes. The androgen receptor appears to be a transcription factor, regulated by androgenic steroids. Phosphorylation is the predominant cellular mechanism for reversible modification of proteins, and the fact that many transcription factors are phosphoproteins suggests a regulatory role of phosphorylation. In this thesis, studies on phosphorylation of the androgen receptor in human prostate tumor cells (LNCaP) are described. In LNCaP cells, the androgen receptor protein is present as two isofonlls with apparent molecular masses of 110 and 112 kDa during SDS-PAGE. The 112 kDa isoform reflects the phosphorylated receptor, whereas the 110 kDa isoform is the non-phosphorylated receptor. Both isoforms are able to bind androgens with high affinity and can subsequently be transformed to the DNA binding form. It appears to be unlikely that phosphorylation is involved in the regulation of steroid- or DNA binding affinity. Upon incubation of the prostate tumor cells with androgens, the phosphOlylation degree of the androgen receptor was rapidly increased. Multiple phosphorylation sites on serine residues are located in the N-terminal f/'al/~activation domain and not in the DNA- and ligand binding domains. Tryptic phosphopeptide maps of the androgen receptor show induction of phosphorylation at a novel site(s) by hormone treatment. It is proposed that this extra phosphorylation in the N-terminal domain causes a conformational change, enabling protein-protein contacts of the trails-activation domain with other transcription factors or co-activators on a target gene promoter.