The O6-alkylation of guanine residues in DNA treated with alkylating agents induce mutations due to mis-pairing resulting from the deprotonation of N1. In addition to the deprotonation of N1, the conformation of the O6-alkyl group with respect to N7 of guanine is very important. Here, we present X-ray crystallographic evidence that shows that the methyl group in O6-methylguanosine has a preference for the distal conformation, blocking the Watson-Crick sites. This distal conformation persists in the solid state for several analogs of O6-alkylguanosine also. This preferred conformation agrees with the result that poly(O6-methyl GMP) does not form any stable complex with poly(U). However, the mispairing of O6-methylguanine with thymine and the resultant G----A transition is known from in vitro studies. The above two opposite results strongly indicate that the conformation of the O6-alkyl group and the base pairing properties of O6-alkylguanine at the monomer and polymer levels must be different from the situation when the modified base is embedded with a small frequency in a duplex. It is interesting to note that the sterical blocking of the Watson-Crick site at the monomer level and the altered base pairing properties when present as occasional bases in a duplex emerge as a common property for several mutagenic bases like O6-alkylguanines, O4-methyluracil and N4-hydroxycytosine.