Well over 100 isolates of granulosis viruses (GVs), genus Granulovirus (family Baculoviridae), have been reported, all from lepidopterous insects. Three types of GVs are recognized, those of Type 1, which attack the fat body, Type 2, which attack most tissues, and Type 3, which attack only the midgut epithelium. To determine whether a correlation exists between tissue tropism and lepidopteran family phylogeny, the granulin gene of the Harrisina brillians (HbGV), a virus that attacks the midgut epithelium of H. brillians (family Zygaenidae) was cloned, sequenced, characterized, and compared with granulin genes of GVs that attack species of Tortricidae, Pieridae, and Noctuidae. The HbGV granulin gene encoded a peptide of 248 amino acids with a predicted Mr of 29.6 kDa, and shared a significant level of homology with other granulin (81-95% identical and 90-98% similar) and polyhedrin (49-58% identical and 62-72% similar) proteins. Phylogenetic analyses based on granulin and polyhedrin genes as well as on their 5'-untranslated sequences (5'-UTSs) indicated that HbGV was more closely related to GVs isolated from the tortricids, Cryptophlebia leucotreta (ClGV), Cydia pomonella (CpGV) and Choristoneura fumiferana (CfGV) than to other GVs and NPVs. This analysis provides preliminary evidence for a correlation between GV tissue tropism and the phylogeny of lepidopteran families, suggesting that GVs attacking species of Tortricidae and Zygaenidae are ancestral to those attacking species of the family Noctudiae.