The question of how sequence-specific transcription factors access their cognate sites in nucleosomally organized DNA is discussed on the basis of genomic footprinting data and chromatin reconstitution experiments. A classification of factors into two categories is proposed: (i) initiator factors which are able to bind their target sequences within regular nucleosomes and initiate events leading to chromatin remodelling and transactivation; (ii) effector factors which are unable to bind regular nucleosomes and depend on initiator factors or on a pre-set nucleosomal structure for accessing their target sequences in chromatin. Studies with the MMTV promoter suggest that the extent and number of protein-DNA contacts determine whether a factor belongs to one or the other category. Initiator factors have only a few DNA contacts clustered on one side of the double helix, whereas effector factors have extensive contacts distributed throughout the whole circumference of the DNA helix. Thus, the nature of DNA recognition confers to sequence-specific factors their specific place in the sequential hierarchy of gene regulatory events.