The interferon (IFN)-inducing capacities of intact NDV virions, beta-propiolactone-inactivated particles and several structural components were compared, using human PBML as the IFN producing cells. Intact and inactivated virions as well as the nucleocapsid fraction did not differ significantly in their IFN-inducing capacity. In contrast, genomic RNA as well as M protein fraction and envelopes induced IFN titres to a level of about 10% of those achieved with virions. NDV-induced IFN production could be blocked specifically by incubation with polyclonal anti-NDV-monoclonal antibodies (mAbs) and with two of three anti-HN-mAbs, but not with anti-NDV-mAbs directed against the F, M or NP protein. In addition, IFN induction by fixed MDBK cells, expressing NDV surface proteins after infection with NDV Ulster, was inhibited by one of two anti-F-mAbs. The results suggest that the induction of IFN synthesis in human PBML is a complex process involving not only the HN protein but also the uncleaved F protein precursor, a component of the M protein fraction and--once having entered the cell--the genomic RNA.