THE human immunodeficiency virus (HIV) matrix protein, p17, forms the outer shell of the core of the virus, lining the inner surface of the viral membrane1-4. The protein has several key functions. It orchestrates viral assembly via targeting signals that direct the gag precursor polyprotein, p55, to the host cell membrane1,5-7 and it interacts with the transmembrane protein, gp41, to retain the env-encoded proteins in the virus8. In addition, pi7 contains a nuclear localization signal that directs the preintegration complex to the nucleus of infected cells9. This permits the virus to infect productively non-dividing cells, a distinguishing feature of HIV and other lentiviruses. We have determined the solution structure of p17 by nuclear magnetic resonance (NMR) with a root-mean square deviation for the backbone of the well-defined regions of 0.9 Å. It consists of four helices connected by short loops and an irregular, mixed β-sheet which provides a positively charged surface for interaction with the inner layer of the membrane. The helical topology is unusual; the Brookhaven protein database contains only one similar structure, that of the immune modulator interferon-γ.