Intravenous immunoglobulin (IVIG) therapy has represented a major advance in the treatment of patients with primary immune deficiency disorders. In September 2000 a new IVIG formulation, Intragam P, was introduced into clinical use. Intragam P is prepared by delipidation of pooled plasma followed by an ion exchange chromatography step to eliminate immunoglobulin aggregates. It is then pasteurized for 10 h at 60 degrees C for viral inactivation before storage at pH 4.25 in 10% maltose. We report initial clinical experience with this new preparation. The details of adverse reactions of patients who received the new preparation were gathered shortly after it became apparent there was a change in IVIG formulation. Seven of 49 patients receiving Intragam P spontaneously reported adverse effects, which were temporally related to infusions. Subsequently, all seven patients have been able to tolerate the product with prophylactic use of antihistamines and paracetamol. This case series indicates that long-term tolerance of an older IVIG product does not necessarily equate to tolerance to a newer product, even if technically superior. Caution should be exercised when changing IVIG products, as they are not biologically equivalent.