The synthesis of 4-amino-1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin-7 (6H)-one (3) from the reaction of ethyl 3-cyano-1-beta-D-ribofuranosylpyrrole-2-carboxylate (10) and hydrazine is described. The 5:6 pyrrolo[2,3-d]pyridazin-7(6H)-one structure of 3 was established via a three-step conversion of 3 into 1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin-4,7(5H,6H)- dio ne (14). 4-Amino-3-chloro-1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin+ ++-7(6H)-one (16) 4-amino-3-bromo-1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin++ +-7(6H)-one (18) were prepared via N-chlorosuccinimide or N-bromosuccinimide treatment of 4-amino-1-(2,3,5-tri-O-benzyl-beta- D-ribofuranosyl)pyrrolo[2,3-d]pyridazin-7(6H)-one (7) followed by a removal of the benzyl groups with boron trichloride. Direct treatment of 3 with N-iodosuccinimide furnished 4-amino-3-iodo-1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin -7(6H)-one (19). The antiproliferative activity of the compounds was determined in L1210, H. Ep. 2 and several additional human tumor cell lines. In L1210 cells, the 3-halo-substituted compounds 16, 18, and 19 exhibited significant cytotoxicity (IC50 = 0.2, 0.1, 0.08 microM, respectively), in contrast to the 3-unsubstituted compound 3, which had only slight activity. The greater antiproliferative activity of 18 and 19 in contrast to 3 was confirmed in H. Ep. 2 cells and KB cells. The antiviral evaluation of these compounds revealed that compounds 16, 18, and 19 were active against human cytomegalovirus in both plaque- and yield-reduction assays. However, this activity was only partially separated from cytotoxicity in human cell lines.