Water‐permeable membranes of several plant and mammalian tissues contain specific water channel proteins, the ‘aquaporins’. The best characterized aquaporin is CHIP, a 28 kDa red blood cell channel‐forming integral protein. Isolated CHIP and Escherichia coli lipids may be assembled into 2‐D crystals for structural analyses. Here we present (i) a structural characterization of the solubilized CHIP oligomers, (ii) projections of CHIP arrays after negative staining or metal‐shadowing, and (iii) the 3‐D structure at 1.6 nm resolution. Negatively stained CHIP oligomers exhibited a side length of 6.9 nm with four‐fold symmetry, and a mass of 202 +/‐ 3 kDa determined by scanning transmission electron microscopy. Reconstituted into lipid bilayers, CHIP formed 2‐D square lattices with unit cell dimensions a = b = 9.6 nm and a p422(1) symmetry. The 3‐D map revealed that CHIP tetramers contain central stain‐filled depressions about the fourfold axis. These cavities extend from both sides into the transbilayer domain of the molecule leaving only a thin barrier to be penetrated by the water pores. Although CHIP monomers behave as independent pores, we propose that their particular structure requires tetramerization for stable integration into the bilayer.