We present current progress on the SAPHIR project, an open-source, modular modeling environment of cardiovascular and respiratory physiology using state-of-the-art multi-scale simulation methods. Our model initially targets blood pressure and body fluid homeostasis. We present re-implementations of two legacy models that treated overall regulation of blood pressure (Guyton et al. 1972), and fluid regulation (Ikeda et al. 1979). The basic “core model” includes lumped-parameter input-output descriptions of relevant organs as modules, i.e., heart, vasculature, intra- and extracellular spaces, lungs, kidneys, and muscles. This core model can be modified/extended by customizing existing modules or by replacing one or several of the core modules by more detailed, mechanistic models at finer resolution. As modeling/simulation environments, Berkeley-Madonna was used for Ikeda’s model (JF, PB); Fortran (SRT), Matlab/Simulink (PH, FG) and the M2SL C++ software library (Rennes laboratory, AH & VL), were used for implementation of the original Guyton models. M2SL will be the basic solver package for the multi-module modeling environment. The resulting modular modeling environment is compact enough to run on a personal computer and yet accomodate detailed mechanistic submodules. This open-source, modular approach allows for (i) selected extensions/refinements of the model (e.g. addition of a pancreas module and regulation of blood glucose) and (ii) assessment of system-level consequences of local perturbations (e.g. models of functional consequences of genetic polymorphisms). One important goal is to keep the model compact enough to ensure fast execution time (in view of eventual use in clinical settings), yet to allow detailed sub-modules (to maintain system-integrated feedback loops). This approach will eventually provide a platform for patient-specific exploration of therapeutic scenarios in the context of the IUPS Physiome.