Objective: The effects of hapten inhibition with dextran 1 (molecular weight: 1,000 D, Promit®), which is in use since 1982 for the prevention of severe dextran-induced anaphylactic reactions (DIAR) caused by immune complexes, were studied. Design: Spontaneous reports to the manufacturer and to the WHO database INTDIS regarding adverse reactions to clinical dextran after preinjection of dextran 1 and to dextran 1 alone were collected from 1983 to 1992. During this period a total of 5.1 million doses of dextran 1 were sold in 15 countries. Interventions: Analysis of pre- and post-reaction titers of dextran-reactive antibodies (DRA) was made in most Scandinavian reports. Results: The incidence of severe DIAR (grades III-V) to clinical dextran after the prophylactic use of hapten inhibition was approximately 1/200,000 patients receiving dextran 1. In Sweden, where reporting of severe adverse drug reactions is mandatory, the incidence was approximately 1/70,000, indicating a 35-fold reduction. Only 2 fatal reactions were reported, an incidence of 1/2.5 million doses, indicating a 90-fold reduction. Both these occurred in patients with extremely high titers of DRA. Side effects to dextran 1, mostly mild, were reported in approximately 1 case per 100,000 doses. These side effects were not antibody mediated. Conclusions: The above findings, together with other recent safety profile data, suggest that dextran with hapten inhibition has possibly become the safest plasma substitute in current clinical practice.