The spruce budworm is the most economically important destructive insect pest affecting North American forests. Some endophytes isolated from the Acadian forest produce secondary metabolites, toxic to the spruce budworm in planta. The aim of this study was to investigate the biologically active extracts of endophytes of red (Picea rubens) and black spruce (P. mariana). This was hypothesized to result in the isolation of antifungal and antiinsectan metabolites with structural similarities to related pathogenic toxins. From this investigation, 13 secondary metabolites were isolated. Three macrocyclic lactones (1-3) were characterized from Nectria dacryocarpa. Six aromatic metabolites (4-9) were isolated from two unique species of Penicillium cf. glaucoalbidum belonging to the Thysanophora sect. Four lachnellulone related compounds (10-13) were isolated from Lachnellula cf. calyciformis including new compounds (12, 13). Most purified secondary metabolites inhibited the growth of test microorganisms in vitro, including Saccharomyces cerevisiae, Bacillus subtilis, Escherichia coli, and Microbotryum violaceum.