The hyperimmunoglobulinaemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent unpredictable febrile attacks with abdominal pain, joint involvement (arthralgias/arthritis), headache, skin lesions and a polyclonal elevation of serum IgD (> 100 U mL-1). Interferon-gamma (IFN-gamma) is a major proinflammatory cytokine which could play a role in the pathogenesis of the attacks. There is a need for parameters (if possible non-invasive) to monitor disease activity. A potential candidate is neopterin which is released by monocytes/macrophages when stimulated with IFN-gamma, excreted unchanged in urine, and appears to be an early and sensitive marker for activation of the immune system. We measured rectal body temperature, serum IFN-gamma, and urine neopterin in 10 hyper-IgD patients both during and between attacks. The body temperature rose to a mean of 38.9 degrees C on the first day of the attack and normalized within 5 days. Serum IFN-gamma during the first day of the attack was 2.98 IU mL-1 and was significantly lower during remissions. The urine neopterin excretion was 268 +/- 170 mumol mol-1 creatinine between attacks and was significantly increased to 638 +/- 275 mumol mol-1 creatinine on the first day of symptoms. Maximal urine neopterin values were reached on the fourth day of the attack (1051 +/- 387 mumol mol-1 creatinine) and excretion gradually declined and attained values below 400 mumol mol-1 creatinine after 9 days. There was a good correlation between serum IFN-gamma and urine neopterin.(ABSTRACT TRUNCATED AT 250 WORDS)