The anti-HIV effects of a derivative of the CC chemokine RANTES, which lacks chemotactic and leukocyte-activating properties and acts as a receptor antagonist, were investigated. Results showed that structural modification of a chemokine can yield a variant lacking chemotactic and leukocyte-activating properties, but still retaining high affinity for chemokine receptors and the ability to block HIV infection. It is suggested that receptor signalling and cell activation are probably not required for the anti-HIV effect of chemokines, and that blockade of the receptor may be sufficient.