Insights into details of the biomechanism by which porphobilinogen (1) cyclotetra-merizes to uroporphyrinogen III (2) as well as prom ising synthetic applications are provided by investigation of this reaction in vitro . The cyclotetramerization of newly prepared norporphobilinogen (5) proved to be extremely specific due to strong conformational control. Advantage was taken of this finding by preparing a N, N, N, N - tetramethyl-porphyrinogen (13a) for the first time. Protected derivatives of the linear tetramer of porphobilinogen (20c) which is regarded as an intermediate of the cyclotetramerization were gained by total synthesis and their transformations investigated.