The N-terminal transactivation domain of the E2 protein from human papillomavirus type 16 has been crystallized by vapour diffusion. Crystals belong to the space group P3₁21 (or P3₂21) with unit-cell dimensions a = b = 54.3, c = 155.5 Å. There is one molecule per asymmetric unit with a solvent content of 55%. Crystals diffract to at least 2.5 Å resolution and complete X-ray data to 3.4 Å have been collected on a conventional laboratory source. This 201- amino-acid domain of the E2 protein has been shown to interact functionally with both the HPV E1 protein and at least three cellular transcription factors, to fulfil its role in the control of viral transcription and replication. A knowledge of the structural basis of these multiple interactions should lead to a fuller understanding of the mechanism of action of this key regulator of the HPV life cycle.