A new equine abortigenic disease, mare reproductive loss syndrome (MRLS), was recognized and significantly impacted the Ohio Valley in the springs of 2001 and 2002. MRLS caused approximately 330 million US dollars in losses in 2001. An epidemiological investigation of MRLS associated occurrence of the disease with exposure to eastern tent caterpillars (M. americanum). This work investigates the epidemiological association between M. americanum and MRLS to determine if this association was correlative or causative. A pilot study and simulated exposure to M. americanum and their excreta on pasture grasses. The pilot study advanced exposure of pregnant mares to M. americanum materials and 18 of the 29 mares in the study aborted with symptoms of MRLS before other cases were reported in the region. In, three of seven mares exposed to M. americanum aborted, while mares in control (n=6) and M. americanum frass (n=7) treatments had no losses. In, mares were fed frozen insect larvae in feed buckets mixed with oats. Abortions occurred in three of five mares receiving frozen M. americanum, while mares that were fed autoclaved M. americanum (n=5) or frozen gypsy moth larvae (n=4) had no abortions due to MRLS. In, M. americanum larvae were dissected and fractionated. Statistically significant numbers of abortions occurred only in the positive control group and in association with the M. americanum exoskeleton. All abortions induced by exposure to M. americanum exhibited changes in echogenicity of fetal fluids and bacteriological findings post abortion that were consistent with MRLS. These studies support the hypothesis that ingestion of M. americanum larvae induces the MRLS-type equine abortions, and provide experimental evidence that this lepidopteran larva can cause an abortigenic disease in a vertebrate host.