OBJECTIVE (1) Provide an overview of the biomechanical factors that are required to analyze and interpret biological data from explant experiments; (2) Present a description of some of the mechano-electrochemical events which occur in cartilage explants during loading. METHODS A thorough and provocative discussion on the effects of loading on articular cartilage will be presented. Five simplest loading cases are considered: hydrostatic pressure, osmotic pressure, permeation (pressure loading), confined compression and unconfined compression. Details of how such surface loadings are converted or transduced by the extracellular matrix (ECM) to pressure, fluid, solute and ion flows, deformation and electrical fields are discussed. RESULTS Similarities and differences in these quantities for the five types of loading are specifically noted. For example, it is noted that there is no practical mechanical loading condition that can be achieved in the laboratory to produce effects that are equal to the effects of osmotic pressure loading within the ECM. Some counter-intuitive effects from these loadings are also described. Further, the significance of flow-induced compression of the ECM is emphasized, since this frictional drag effect is likely to be one of the major effects of fluid flow through the porous-permeable ECM. Streaming potentials arising from the flow of ions past the fixed charges of the ECM are discussed in relation to the flow-induced compaction effect as well. CONCLUSIONS Understanding the differences among these explant loading cases is important; it will help to provide greater insights to the mechano-electrochemical events which mediate metabolic responses of chondrocytes in explant loading experiments.