Cardiac mechanical alternans are believed to be associated with intracellular Ca alternans. Mechanisms underlying Ca alternans are unclear. We have developed a cardiac cell model with 6 μm resolution to study the roles of sarcoplasmic reticulum (SR) Ca content, ryanodine receptor (RyR) opening and Ca waves in the generation of Ca alternans. Each element has a voltage-gated L-type Ca channel, a subspace, a cytoplasm space and SR RyR channel. For each of 25 elements, mathematical equations were developed to model local intracellular Ca cycling. Inter-element coupling was via Ca diffusion between neighbouring subspaces and cytoplasm spaces. We have previously shown under voltage clamp, that small depolarising pulses produce marked alternans of systolic Ca transients (Diaz et al., 2004). We believe this is related to activation of only a few L-type channels and initiation of propagating waves of Ca release from these sites. In simulations small pulses were used to reduce L-type channel opening. To further reduce current 10 out of 25 channels were blocked by 95% in a random pattern in each pulse. Line scans of [Ca]_i were plotted against time and space (Fig. 1). Local and whole cell [Ca]_i, SR Ca content and Na/Ca exchange current (NCX) were measured. The large stimuli produced spatially uniform transients (not shown). The smaller pulse at first produced a very small [Ca]_i transient that then alternated between large and small. This was associated with alternans of SR Ca content. Importantly, Fig. 1B shows that large releases are not spatially uniform. The small pulse activates L-type channels at only a few sites to give Ca release at these points. When SR Ca is high these release sites stimulate their neighbours and a propagating wave is initiated. With a large release a large NCX current follows depleting the SR. So, wave propagation on the next pulse is not possible and only localised Ca sparks are seen. SR refilling can then take place. The simulations are consistent with our experimental observations and show that Ca alternans can be generated and sustained through alternation of SR Ca content produced by wave propagation.