Infection of human epidermoid carcinoma No. 2 cells with herpes simplex virus type 1 (HSV-1) leads to a reorganization of antigens associated with both the small and heterogeneous nuclear ribonucleoprotein complexes (snRNP and hnRNP). The hnRNP core protein antigens remain associated with the host chromatin, which appears to collapse into internal aggregates and along the nuclear envelope. More striking is the formation of prominent clusters of snRNP antigens (both general and U1 snRNP specific), which appear to condense throughout the nucleus then migrate to the periphery. These snRNP clusters have been identified at the fine structure level by immuno-electron microscopy. The HSV-1 presumed transcriptional activator ICP4, DNA-binding protein ICP8, and two capsid proteins ICP5 and p40 are not detectably associated with the snRNP clusters. Similar reorganization of snRNP occurs with HSV-2 and upon infection of African green monkey VERO cells with HSV-1. We speculate that the snRNP clusters arise from an increase in size and density of the interchromatin granule region of the host cell as a result of the partial inactivation of snRNP and host pre-mRNA splicing.