Progesterone 5beta-reductase (5beta-POR) catalyzes the reduction of progesterone to 5beta-pregnane-3,20-dione and is the first stereospecific enzyme in the putative biosynthetic pathway of Digitalis cardenolides. Selenomethionine-derivatized 5beta-POR from D. lanata was successfully overproduced and crystallized. The crystals belong to space group P4(3)2(1)2, with unit-cell parameters a = 71.73, c = 186.64 A. A MAD data set collected at 2.7 A resolution allowed the identification of six out of eight possible Se-atom positions. A first inspection of the MAD-phased electron-density map shows that 5beta-POR is a Rossmann-type reductase and the quality of the map is such that it is anticipated that a complete atomic model of 5beta-POR will readily be built.