Recently, the LD78β isoform of the CC chemokine macrophage inflammatory protein (MIP)‐1α was shown to efficiently chemoattract lymphocytes and monocytes and to inhibit infection of mononuclear cells by R5 HIV‐1 strains. We have now demonstrated that after cleavage of the NH₂‐terminal Ala‐Pro dipeptide by CD26, LD78β(3 – 70) became the most potent chemokine blocking HIV‐1. LD78β(3 – 70) competed tenfold more efficiently than LD78β(1 – 70) with [¹²⁵I] RANTES for binding to the CC chemokine receptors CCR5 and CCR1. Contrary to LD78α, LD78β(1 – 70) at 30 ng / ml efficiently competed with [¹²⁵I] RANTES for binding to CCR3 and mobilized calcium in CCR3 transfectants, whereas LD78β(3 – 70) showed a 30‐fold decrease in CCR3 affinity compared to LD78β(1 – 70). This demonstrates the importance of the penultimate proline in LD78β(1 – 70) for CCR3 recognition. Both LD78β isoforms efficiently chemoattracted eosinophils from responsive donors. In contrast, only the CCR3 agonist LD78β(1 – 70) and not LD78β(3 – 70), induced calcium increases in eosinophils with low levels of CCR1. In responder neutrophils, LD78β(3 – 70) elicited calcium fluxes at a 30‐fold lower dose (10 ng / ml) compared to intact LD78β and LD78α, whereas the three MIP‐1α isoforms were equipotent neutrophil chemoattractants. Taken together, both LD78β isoforms are potent HIV‐1 inhibitors (CCR5) and activators for neutrophils (CCR1) and eosinophils (CCR1, CCR3), affecting infection and inflammation.