Spontaneous cartilage degeneration of the femorotibial joint of male Hartley guinea pigs, 61 to 365 days old, was studied by light microscopy (LM) and scanning electron microscopy (SEM) to determine the incidence, age at onset, and to characterize the early changes. Knee joints of 61 day old animals were histologically and ultrastructurally normal. Focal minimal degeneration characterized by cell and proteoglycan loss with surface fibrillation was first observed by LM on the medial tibial plateau (MTP) in two of five 89 day old animals. Mild lesions characterized by focal surface disruption, primarily in the area of medial tibial plateau not covered by the meniscus, were observed in three of five 89 day old animals by SEM. Light microscopic alterations in knee joints of 4, 5, and 6 month old animals consisted of varying degrees of focal chondrocyte death, decreased toluidine blue matrix staining, and surface fibrillation. Small chondrocytic clones were first observed in medial tibial cartilage of 6 month old animals with moderate focal degeneration. Ultrastructurally, 4, 5, and 6 month old animals generally had moderate to severe fibrillation involving primarily the area of the medial tibial plateau not covered by the meniscus. Tibial osteophyte formation, mild synovial hyperplasia, medial femoral and meniscal cartilage degeneration, were first seen by LM in 9 month old animals. Lesions in 1 year old animals were similar, but more severe and included subchondral sclerosis of medial tibial and femoral bone. Bilateral fibrillation of greater than 50% of the medial tibial articular surface was observed in all 1 year old animals by SEM.(ABSTRACT TRUNCATED AT 250 WORDS)